Amplification of ferroptosis with a liposomal nanoreactor cooperates with low-toxicity doxorubicin apoptosis for enhanced tumor chemotherapy. (16th February 2022)

• Record Type: Journal Article
• Authors: Ji, Peng; Wang, Xianglong; Yin, Jiabing; Yao, Yansheng; Du, Wangqi
• Is Part Of: Biomaterials science. Volume 10:Number 6(2022)
• Page Start: 1544
• Page End: 1553
• Publication Date: 2022-02-16
• Subjects: Biomedical materials -- Periodicals; 610.28
• DOI: 10.1039/d2bm00079b
• Languages: English
• ISSNs: 2047-4830

Abstract

Abstract : Developed a novel DOX/ART@LiMOFs nanoreactor that can combine apoptosis and ferroptosis to realize enhanced chemotherapy. Abstract : Despite the remarkable tumor inhibition effect of doxorubicin (DOX), its cardiotoxicity severely limits the clinical dosage and further impairs the chemotherapy efficacy. To improve the biosafety and effectiveness of conventional chemotherapy, we propose a strategy to co-deliver DOX and ART to supplement apoptosis with ferroptosis. To this end, ART and DOX were incorporated into ferrous LiMOFs to develop a nanoreactor, utilizing ferrous ions as a catalyst to decompose ART into radicals and thus to induce efficient ferroptosis. Further, DOX can induce another form of death, apoptosis, which in combination enhances tumor inhibition. The synthesized nanoreactor (DOX/ART@LiMOFs) possesses a size of ∼100 nm and maintains a regular crystal structure. The pH-responsive disassociation endows it with acid-sensitive drug-releasing kinetics, and the liposomal bilayers bring about a sustained release feature (up to 12 h). The cellular ROS assay indicated that the supply of ferrous ions dramatically increased the ROS mediated by ART and led to markedly enhanced tumor inhibition in animal tests accompanied by the apoptosis of DOX. Consequently, this work presents an innovative strategy to synchronously induce potent ferroptosis and apoptosis, promoting conventional cancer chemotherapy.